Forskolin, a diterpene, activates adenylate cyclase in broken cell preparations as well as in intact tissues. This activation does not require the guanine nucleotide regulatory subunit of the enzyme and probably occurs via an interaction with the catalytic subunit or an associated protein. Activation of adenylate cyclase by forskolin results in marked increases in levels of intracellular cyclic AMP in a variety of eukaryotic cells. Low concentrations of forskolin which alone elicit small increases in intracellular cyclic AMP greatly potentiate hormonal activation of adenylate cyclase in a number of intact cells. Forskolin elicits cellular responses which have been proposed to be dependent on cyclic AMP as a second messenger. Forskolin, thus, provides an invaluable tool for the investigation of the role of cyclic AMP both through its direct activation of adenylate cyclase and through its ability to potentiate activation of adenylate cyclase by biogenic amines, peptides, prostaglandins and adenosine. Activation of adenylate cyclase by calmodulin appears independent of guanyl nucleotides but may be influnced by membrane phosphorylation and its potentiated by forskolin. Striatum appears to contain three classes of adenosine receptors, two of which are stimulatory to adenylate cyclase.